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Mapping ADHD Heterogeneity and Biotypes by Topological Deviations in Morphometric Similarity Networks

Normative modeling of morphometric similarity networks in ADHD identified three distinct biotypes with unique clinical-neural profiles, supporting more neurobiologically informed stratification for ADHD management.


Question Can normative modeling of topological properties derived from brain morphometric similarity networks yield robust stratification biomarkers for pediatric populations with attention-deficit/hyperactivity disorder (ADHD)?

Findings This multisite case-control study included 1,154 participants, characterizing ADHD heterogeneity through hub-centric topological deviations derived from morphometric similarity networks. Three distinct biotypes emerged, each exhibiting unique clinical-neural profiles with characteristic neurochemical and functional correlates, validated in an independent transdiagnostic cohort of 554 ADHD cases.

Meaning The integration of normative modeling with heterogeneity through discriminative analysis (HYDRA) clustering yielded both dimensional and categorical insights into ADHD heterogeneity, thereby enhancing our understanding of the ADHD’s neurobiological complexity.

Nanoparticles for Targeted Drug Delivery to Cancer Stem Cells: A Review of Recent Advances

Cancer stem cells (CSCs) are a subpopulation of cells that can initiate, self-renew, and sustain tumor growth. CSCs are responsible for tumor metastasis, recurrence, and drug resistance in cancer therapy. CSCs reside within a niche maintained by multiple unique factors in the microenvironment. These factors include hypoxia, excessive levels of angiogenesis, a change of mitochondrial activity from aerobic aspiration to aerobic glycolysis, an upregulated expression of CSC biomarkers and stem cell signaling, and an elevated synthesis of the cytochromes P450 family of enzymes responsible for drug clearance. Antibodies and ligands targeting the unique factors that maintain the niche are utilized for the delivery of anticancer therapeutics to CSCs. In this regard, nanomaterials, specifically nanoparticles (NPs), are extremely useful as carriers for the delivery of anticancer agents to CSCs.

Signaling pathways in the regulation of cancer stem cells and associated targeted therapy

The concept of stem cells dates back to the 18th century when scientists tried to elucidate how lower organisms developed tissues and organs. 1 These stem cells produce daughter cells that later undergo different biological processes, either continuous self‐renewal division, or differentiation into specialized cells with a limited lifespan. Normal tissue stem cells provide a life‐long source of cells for self‐renewal of tissues, which leads us to speculate that whether stem cells are capable of deriving a malignant cell population, and this lies the foundation of cancer stem cells (CSCs) theory. CSCs are defined as a subpopulation of malignant tumor cells with selective capacities for tumor initiation, self‐renewal, metastasis, and unlimited growth into bulks. 2

Despite decades of research on cancer treatment, it has been proved extremely challenging to achieve complete remission (CR) in cancer patients. Tumor relapse may be explained by the fact that antitumor therapeutics mainly target proliferative cancer cells but remain ineffective in quiescent CSCs. The role of CSC in tumor initiation was first identified in acute myeloid leukemia (AML). Since its isolation from a number of solid tumors and hematological malignancies, the CSC is believed to form the clonogenic core of these tumors. 3 Growing evidence now suggests that CSCs are responsible for multiple progressive tumor phenotypes, including recurrence, metastasis, and treatment failure. 4, 5 The intrinsic treatment resistance of tumors has partially attributed to the presence of the CSC subpopulation, 6, 7 and may also be induced by extrinsic factors, such as treatments and environments. 8, 9

Major signaling pathways are involved in the maintenance of stem cell properties and survival of CSCs, such as the Notch, Wnt, and Hedgehog (HH) pathways. 10 There is also intricate interplay network between these signal cascades and other oncogenic pathways. 11, 12, 13 Thus, targeting pathway molecules that regulate CSCs provides a new option for the treatment of therapy‐resistant or ‐refractory tumors. This review aims to provide an overview of the regulating networks and their immune interactions involved in CSC development. We also summarized the update on the development of CSC‐directed therapeutics, with a special focus on those with application approval or under clinical evaluation.

An agentic system for rare disease diagnosis with traceable reasoning

DeepRare—a multi-agent system for rare disease differential diagnosis decision support powered by large language models, integrating specialized tools and up-to-date knowledge sources—has the potential to reduce healthcare disparities in rare disease diagnosis.

Associations of Lifetime Cognitive Enrichment With Incident Alzheimer Disease Dementia, Cognitive Aging, and Cognitive Resilience

Study results suggest that cognitive health in later life is in part the product of lifetime exposure to cognitive enrichment.


Background and Objectives.

A Reflection on Movement Disorders Fellowship Training in Deep Brain Stimulation: Past and Future

A Reflection on Movement Disorders —Fellowship Training in Deep Brain Stimulation: Past and Future.


Deep brain stimulation (DBS) has been an integral part of movement disorders care for decades. However, differences exist in techniques for surgical implantation of DBS and clinician experience with DBS systems, including use of new software, programming approaches, and postsurgical management of patients. DBS technologies have been rapidly advancing, and indications for DBS are increasing, including for psychiatric symptoms and epilepsy. The heterogeneity in the scope and utility of DBS is perhaps mirrored in education and training, despite efforts to develop competency measures for trainees. These advancements in DBS and the varying opportunities offered at each fellowship contribute to challenges for program directors to establish and implement consistent expectations. Similar challenges have been observed in other fields using neuromodulation.

Scientists reverse muscle aging in mice and discover a surprising catch

A UCLA study in mice reveals that aging muscle stem cells accumulate a protein that slows repair but boosts survival. This protein, NDRG1, acts like a brake, preventing cells from activating quickly after injury. When researchers blocked it in older mice, muscle healing sped up dramatically — but stem cells became less resilient over time. The work suggests aging may reflect a survival trade-off rather than straightforward decline.

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